Peptic ulcer
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A benign gastric ulcer (from the antrum) of a gastrectomy specimen. |
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Endoscopic image of gastric ulcer, biopsy proven to be gastric cancer. |
A
peptic ulcer is an
ulcer of one of those areas of the
gastrointestinal tract that are usually acidic. A more general term,
peptic ulcer disease (PUD), is also in use.
Most ulcers are associated with
Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach. Ulcers can also be caused or worsened by drugs such as
Aspirin and other
NSAIDs. Contrary to general belief, more peptic ulcers arise in the
duodenum (=first part of the
small intestine, just after the stomach) than in the
stomach. About 4 % of stomach ulcers are caused by a malignant tumour, so multiple biopsies are needed to make sure. Duodenal ulcers are generally non-
malignant.
A peptic ulcer may arise at various locations:
*
Stomach (called
gastric ulcer)
*
Duodenum (called
duodenal ulcer)
*
Esophagus (called
esophageal ulcer)
* A
Meckel's diverticulumSymptoms of a peptic ulcer can be:
*
Abdominal pain, classically epigastric with severity relating to mealtimes (duodenal ulcers are classically relieved by food, while gastric ulcers are exacerbated by it);
* Bloating and abdominal fullness
*
Waterbrash (bitter regurgitation)
* Nausea, and sometimes vomiting
* Loss of appetite and weight loss;
*
Hematemesis (vomiting of blood);
*
Melena (tarry, foul-smelling feces due to
oxidised iron from
hemoglobin);
* Rarely, an ulcer can lead to a gastric or duodenal perforation. This is extremely painful and requires immediate surgery.
A history of
heartburn,
gastroesophageal reflux disease (GERD) and use of certain forms of medication can raise the suspicion for peptic ulcer. Medicines associated with peptic ulcer include
NSAID (non-steroid anti-inflammatory drugs) that inhibit
cyclooxygenase, and most
glucocorticoids (e.g.
dexamethasone and
prednisolone).
In patients over 45 with more than 2 weeks of the above symptoms the odds for peptic ulceration are high enough to warrant rapid investigation by EGD (see below).
The timing of the symptoms in relation to the meal may differentiate between
gastric and
duodenal ulcers: A gastric ulcer would give
epigastric pain during the meal, as
gastric acid is secreted, or
after the meal, as the alkaline duodenal contents reflux into the
stomach. Symptoms of duodenal ulcers would manifest mostly
before the meal — when acid (production stimulated by hunger) is passed into the
duodenum.
Despite the finding that a
bacterial infection is the proximate cause of ulcers in 75% of cases, support for the theory that stress causes ulcers has not disappeared.
*The experts looked over the evidence and concluded that ulcers are not merely an
infectious disease and that psychological factors do play a significant role. [
1]
One researcher said,
*Having a
positive attitude seems to correlate with an increased ability of the
immune system in fighting diseases.[
2]
According to research physician Susan Levenstein,
*I have a suspicion that one reason the medical establishment wiped stress off the charts so fast was that it didn't feel comfortable with
psychological explanations. They were happier when they could label ulcers as an infectious disease. It's easy to fall into either-or thinking: either ulcers are caused by stress or they're caused by Helicobacter. The truth is much more complicated and, I think, more exciting. Since peptic ulcer is one of the few 'infectious' diseases in which stress plays an important role, it gives us a great model for understanding how psychological factors can tip the balance toward disease, in the uneasy equilibrium we all live in with a whole variety of infectious agents. [
3]
*The discovery that Helicobacter pylori is a cause of peptic ulcer has tempted many to conclude that psychological factors are unimportant. But this is dichotomised thinking. There is solid evidence that
psychological stress triggers many ulcers and impairs response to treatment, while helicobacter is inadequate as a monocausal explanation as most infected people do not develop ulcers. Psychological stress probably functions most often as a cofactor with H pylori. It may act by stimulating the production of
gastric acid or by promoting behaviour that causes a risk to health. Unravelling the aetiology of peptic ulcer will make an important contribution to the
biopsychosocial model of disease. [
4]
Tobacco smoking,
blood group,
spices and other factors that were suspected to cause ulcers until late in the 20th century, are actually of relatively minor importance in the development of peptic ulcers.
[For nearly 100 years, scientists and doctors thought that ulcers were caused by stress, spicy food, and alcohol. Treatment involved bed rest and a bland diet. Later, researchers added stomach acid to the list of causes and began treating ulcers with antacids. National Digestive Diseases Information Clearinghouse]A major causative factor (75% of gastric and 90% of duodenal ulcers) is chronic
inflammation due to
Helicobacter pylori, a
spirochaete that colonizes (
i.e. settles there after entering the body) the
antral mucosa. The immune system is unable to clear the infection
[Blaser MJ, Atherton JC. Helicobacter pylori persistence: biology and disease. J Clin Invest 2004; 113: 321-33. ], despite the appearance of antibodies. Thus, the
bacterium can cause a chronic active
gastritis (type B gastritis), resulting in a defect in the regulation of
gastrin production by that part of the stomach, and gastrin secretion is increased.
Gastrin, in turn, stimulates the production of
gastric acid by parietal cells. The acids erodes the
mucosa and causes the ulcer.
Another major cause is the use of
NSAIDs (see above). The gastric mucosa protects itself from
gastric acid with a layer of mucous, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the function of
cyclooxygenase 1 (
cox-1), which is essential for the production of these prostaglandins. Newer NSAIDs (
celecoxib,
rofecoxib) only inhibit
cox-2, which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration.
Glucocorticoids lead to atrophy of all
epithelial tissues. Their role in ulcerogenesis is relatively small.
Stress in the psychological sense has not been proven to influence the development of peptic ulcers.
[The majority of peptic ulcers are caused by the H. pylori bacterium. Many of the other cases are caused by NSAIDs. None are caused by spicy food or stress. [5]] Burns and
head trauma, however, can lead to "stress ulcers", and it is reported in many patients who are on
mechanical ventilation.
Smoking leads to
atherosclerosis and vascular spasms, causing vascular insufficiency and promoting the development of ulcers through
ischemia.
A
family history is often present in duodenal ulcers, especially when
blood group O is also present. Inheritance appears to be unimportant in gastric ulcers.
Gastrinomas (
Zollinger Ellison syndrome), rare gastrin secreting tumors, cause multiple and difficult to heal ulcers.
In patients in whom
peptic ulcer is suspected, the correct test is
esophagogastroduodenoscopy (EGD), a form of
endoscopy, sometimes known as just
gastroscopy. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.
The diagnosis of
Helicobacter pylori can be by:
*Biopsy during EGD;
*Breath testing (does not require EGD);
*Direct culture from an EGD biopsy specimen;
*Direct detection of
urease activity in a biopsy specimen;
*Measurement of
antibody levels in
blood (does not require EGD). It is still somewhat controversial whether a positive antibody without EGD is enough to warrant eradication therapy.
The possibility of other causes of ulcers, notably
malignancy (
gastric cancer) needs to be kept in mind. This is especially true in ulcers of the
greater (large) curvature of the
stomach; most are also a consequence of chronic
H. pylori infection.
If a peptic ulcer perforates, air will leak from the inside of the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to "free gas" within the peritoneal cavity. If the patient stands erect, as when having a chest X-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease.
Macroscopical appearance
Gastric ulcer is most often localized on the lesser curvature of the stomach. It is a round to oval parietal defect ("hole"), 2 to 4 cm diameter, with a smooth base and perpendicular borders. These borders are not elevated or irreguliar as in gastric cancer - ulcerative form. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring.
Microscopical appearance
Gastric peptic ulcer is a mucosal defect which penetrates the
muscularis mucosae and muscularis propria, produced by acid-pepsin aggression. Ulcer margins are perpendicular and present chronic gastritis. During the active phase, the base of the ulcer shows 4 zones: inflammatory exudate, fibrinoid necrosis, granulation tissue and fibrous tissue. The fibrous base of the ulcer may contain vessels with thickened wall or with thrombosis.
1Younger patients with ulcer-like symptoms are often treated with
antacids or
H2 antagonists before EGD is undertaken.
Bismuth compounds may actually reduce or even clear organisms.
When
H. pylori infection is present, the most effective treatments are combinations of 2 antibiotics (e.g.
Erythromycin,
Ampicillin,
Amoxicillin,
Tetracycline,
Metronidazole) and 1
proton pump inhibitor (PPI). An effective combination would be
Amoxicillin +
Metronidazole +
Pantoprazole (a PPI). In the absence of
H. pylori, long-term higher dose PPIs are often used.
Treatment of
Helicobacter usually leads to clearing of infection, relief of symptoms and eventual healing of ulcers. Recurrence of infection can occur and retreatment may be required, if necessary with other antibiotics. Since the widespread use of PPI's in the
1990s, surgical procedures (like "highly selective
vagotomy") for uncomplicated peptic ulcers became obsolete.
Perforated peptic ulcer is a surgical emergency and requires surgical repair of the perforation. And most bleeding ulcers require endoscopy urgently to stop bleeding with cautery or injection.
In Western countries the
prevalence of
Helicobacter pylori infections roughly matches age (i.e., 20% at age 20, 30% at age 30, 80% at age 80 etc). Prevalence is higher in
third world countries. Transmission is by food and human contact, sharing food utensils etc.
A minority of cases of
Helicobacter infection will eventually lead to an ulcer and a larger proportion of people will get non-specific discomfort,
abdominal pain or
gastritis.
In 1997, the
Centers for Disease Control and Prevention, with other government agencies, academic institutions, and industry, launched a national education campaign to inform health care providers and consumers about the link between
H. pylori and ulcers. This campaign reinforced the news that ulcers are a curable infection, and the fact that health can be greatly improved and money saved by disseminating information about H. pylori.
[Ulcer, Diagnosis and Treatment - CDC Bacterial, Mycotic Diseases]Helicobacter pylori was rediscovered in 1982 by two
Australian scientists
Robin Warren and
Barry Marshall. In their original paper, Warren and Marshall contended that most stomach ulcers and gastritis were caused by colonization with this bacterium, not by
stress or
spicy food as had been assumed before
.
John Lykoudis was a
general practitioner in
Greece who treated patients from
peptic ulcer disease with
antibiotics long before it was commonly recognized that
bacteria were a dominant cause for the disease
[Basil Rigas, Efstathios D. Papavasassiliou. John Lykoudis. The general parctitioner in Greece who in 1958 discovered the etiology of, and a treatment for, peptic ulcer disease. in Barry Marshall (editor), Helicobacter Pioneers. Firsthand accounts from the scientists who discovered helicobacters, 1892-1982, 2002, ISBN 0867930357.].
*
Pathology specimen of Gastric ulcer*
Pathology of Peptic Ulcer
